Edema, the abnormal or excessive retention of fluid at a site in the body, can produce damaging stress on the body and inhibit proper functioning of organs. Edema inhibits blood flow in tissue, raises systemic blood pressure and otherwise impairs healthy body function. It is often associated with low blood flow and its attendant problems and can affect any location or organ of the body. When excessive fluid collects in tissue there is a need to mitigate the condition to avoid related adverse physiological effects and as an aid to treatment of underlying conditions.
Edema produces swelling which can result in a constriction of blood flow to an affected area. This can place stress on the heart, kidneys, brain, muscle tissue and other organs. Causes of edema include trauma, burns, hypersensitive reactions, thrombophlebitis and disease. Edema can even result from malnutrition, obesity and lack of exercise. In the heart, edema can produce heart failure. Cardiac edema increases the volume of the heart wall; the wall thickens and reduces the volume of the chambers of the heart. Cardiac output is reduced and the workload of the heart is increased. In muscle tissue edema can produce compartment syndrome. Injury can cause a volume of tissue to retain excess fluid and swell. The volume of the swelling tissue is constrained by surrounding tissue so that blood supply to the tissue is restricted.
Water content of tissue can change from time-to-time, and sometimes rapidly so there is a need for an edema monitor which can detect tissue water content in any tissue or organ of the body and monitor it continuously.
Head trauma often results in brain edema and a need to monitor. Serious head injury is almost always associated with excessive fluid retention in brain tissue and brain swelling. As the brain swells the increase in tissue volume is confined by the rigid cranial cavity. The resulting pressure increase restricts blood supply and, if not relieved, produces brain damage.
It has been reported that over 270,000 people in the US are hospitalized for traumatic brain injury each year from vehicular crashes, falls, assaults and other reasons and of these 50,000 to 100,000 deaths occur per year, representing approximately one third of all traumatic brain injuries. In addition, brain injury occurs as a result of subarachnoid hemorrhage and intra-cerebral hemorrhage, afflicting approximately 100,000 people each year in the US. Costs associated with treatment, hospitalization and rehabilitation after traumatic brain injury is estimated at $48.3 billion annually.
Brain trauma induces primary and secondary injury processes. Secondary injury can be due to ischemia and can initiate of a cascade of pathophysiological and biochemical events leading to necrosis, apoptosis and inflammation. Subarachnoid, intraventricular or intraparenchymal hemorrhage can result in focal or diffuse cerebral edema.
Brain edema also occurs to varying degrees in acute traumatic brain injury, hyponatremia (e.g., liver failure), cardiac arrest, and stroke. Brain edema could also occur in chronic conditions such as tumor progression and secondary to cerebral ischemia or hypertensive encephalopathy. The resulting effects of cerebral edema can be deadly. Increased edema volume in the confined space of the cranium increases intracranial pressure which can lead to complete cessation of the cerebral circulation and brain death. The brain can suffer irreversible damage after seven to eight minutes of oxygen deprivation. It has little energy reserves and is highly sensitive to decreased perfusion or oxygen levels.
Since the brain is in a closed space (the cranium), cerebral edema (swelling) causes the intracranial pressure (ICP) to increase. The pressure that drives blood through the capillary beds or the cerebral perfusion pressure (CPP) is the mean arterial blood pressure (MAP) minus the ICP:CPP=MAP−ICP  (1)
Assuming mean arterial blood pressure (MAP) stays relatively constant, an increase in edema and intracranial pressure (ICP) will consequently cause a decrease in cerebral perfusion pressure (CPP) and cerebral blood flow (CBF). This will reduce the oxygen supply to the brain, increase anaerobic metabolism, deplete the glucose supply, release hydrogen ions, and induce intracellular lactic acidosis and brain edema. This leads to a vicious circle of decreasing cerebral blood flow and increasing edema. Ischemia with CBF<18 ml/100 g/min in the first six hours after the primary injury correlates with poor patient outcome. Of note, approximately 80% of severe head injury deaths are caused by secondary injuries. Therefore the detection and reversal of secondary brain ischemic injury is the goal of traumatic brain injury treatment strategies after the immediate effects of the primary injury have been addressed.
Currently, intracranial pressure is among the most commonly monitored variables in cases of head injury. According to the Brain Trauma Foundation, intracranial pressure is monitored in about 78% of neurosurgical intensive care units. Intracranial pressure can be monitored through a ventriculostomy or with an intraparenchymal catheter placed through a burr hole and secured via a bolt. Intracranial pressure (ICP) is used with mean arterial pressure (MAP) to obtain cerebral perfusion pressure (CPP) which represents the pressure gradient across the cerebrovascular bed (see Equation 1).
Numerous techniques have been proposed that attempt to determine if the brain is getting adequate oxygen and a few techniques have attempted to predict the evolving status of cerebral tissue including the presence and magnitude of edema. CT can be used to qualitatively assess water content, but it is not routinely performed at the bedside. MR techniques have been used to quantitatively assess water content, but MR also does not lend itself to routine, bedside monitoring.
Intracranial pressure remains the standard for neuro-monitoring of brain injured patients. Intracranial volume is made up of three components, cerebral blood volume (CBV), cerebrospinal fluid (CSF) volume and brain tissue volume which is subject to brain edema volume. An increase in intracranial pressure is the direct and eventual result of a combination of cerebral edema volume and increased cerebral blood volume (CBV). By the time intracranial pressure starts to increase to pathological levels, brain edema and cerebral blood volume have already progressed to the point where all the available space in the cranium is occupied. As a result, therapy has to rapidly follow any substantial increase in intracranial pressure, making the patient care regimen, very reactive.
Treatment strategies in the management of high intracranial pressure, usually a Consequence of brain edema and increased cerebral blood volume, are guided by two primary concepts. One approach is to target cerebral perfusion pressure where it is progressively increased in order to maintain cerebral blood flow and thereby increase oxygen delivery. However, if an increase in cerebral perfusion pressure elicits an increase in intracranial pressure as may occur where there is loss of autoregulation, then increasing cerebral perfusion pressure is not an option as intracranial pressure will also increase and brain herniation may occur. Thus, alternate interventions sometimes used involve the use of drugs such as beta adrenergic blockers, alpha one agonists, barbiturates and sedatives to target the reduction of intracranial pressure rather than increasing cerebral perfusion pressure.
The most commonly used methods to decrease and maintain intracranial pressure and ameliorate the effect of edema is to drain cerebrospinal fluid (CSF), which leaves more cranial space to be occupied by swelling brain tissue, and to administer osmotic diuretics, such as mannitol or hypertonic saline, which remove water from the tissue and counteract the effects of edema. Cranial perfusion pressure can be increased by increasing mean arterial blood pressure using vasopressors. The use of hypertensive agents, however, remains very controversial. High cranial perfusion pressure may also increase intracranial pressure through edema formation by increased transcapillary filtration. Also vasoconstrictors, which increase mean arterial blood pressure, may decrease cerebral blood flow due to the increased vascular resistance.
In general, the effect of therapies on edema, intracranial pressure and cerebral blood flow may vary from patient to patient. Intracranial pressure is routinely and continuously monitored in patients with severe head injury, cerebral blood flow is increasingly being used in the clinic, but there is no available device to monitor cerebral edema in real time and at the bedside. There is a need for quantitative continuous or near-continuous monitoring. There is a need to improve that capability, quantify brain water content and further to separate intra vascular water from extra vascular water.